Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications in the US. The majority of individuals (55%) receiving SSRIs for treatment of their depression are between the ages of 18 and 50. Thus, clinical depression commonly occurs and is treated concurrent with the reproductive years in an individual's life. Recent statistics suggest that at least 2.5 million men of reproductive age are exposed to SSRI therapy annually. In spite of the large number of individuals taking SSRIs, there is currently little information on their potential impact on sperm function, and specifically on sperm chromatin (DNA) integrity. A critical role of sperm chromatin integrity in normal reproduction has been recognized. Specifically; sperm with high levels of chromatin damage can lead to fertility disorders including: infertility, early embryonic losses spontaneous abortions, and even possible pathology in children. Recent preliminary data by the PI and others suggest a possible risk to sperm chromatin integrity for patients on SSRI therapy. Therefore, we hypothesize that SSRI therapy deleteriously affects sperm chromatin integrity in reproductive age men. A pilot study is proposed which aims to evaluate sperm chromatin integrity before and during SSRI therapy in clinically depressed male patients (treated group) versus depressed male patients undergoing psychotherapy alone (control group). In addition, other aspects of sperm function such as cell numbers and motility, as well as levels of sexual dysfunction and hormone concentrations will also be compared for these two groups of men. This proposal offers a unique interdisciplinary approach, combining expertise in clinical psychopharmacology and reproductive physiology to evaluate the impact of a commonly prescribed SSRI on sperm chromatin quality, and to determine if a patient profile exists for those men most at risk of such sperm chromatin damage during SSRI therapy.